Retinal Organoids: An Emerging Technology for Retinal Disease Research and Therapy

Abstract

Retinal cell replacement is a promising therapeutic approach to restore vision to millions of people worldwide. Three-dimensional culture methods can produce large numbers of human embryonic retinal cells from pluripotent stem cells (PSCs), stimulating optimism for clinical use. These cells develop in a tissue environment that recapitulates many aspects of development in vivo. Most notably, the retinal progenitor cells are competent to give rise to all major retinal cells types, which segregate to rudimentary retinal layers. The cells are expected to mimic their natural counterparts at the molecular level, but that has yet to be demonstrated. These methodologies can produce impressive embryonic retinal structures, but will require optimization before meeting clinical needs. Using current methods PSC-derived retinal organoids do not fully mature, suggesting that the in vitro environment does not reproduce that of late fetal development. However, studies to date suggest that immature photoreceptor or retinal ganglion cells, roughly those of mid-gestation, function best for transplantation. This developmental stage appears to be well reproduced in vitro, and therefore the PSC-derived retinal cells may be appropriate for cell replacement approaches. Three-dimensional culture methods using PSC-derived cells offer hope to better understand and treat retinal disease.